The formation of bone where it is neither needed nor wanted can lead to devastating consequences. Fibrodysplasia Ossificans Progressiva (FOP, OMIM 135100), also known as Myositis Ossificans Progressiva, is the most severe and disabling disorder of extra-skeletal (heterotopic) ossification in humans. Heterotopic ossification in FOP begins in childhood and can be induced by trauma, or may occur without warning. Bone formation is episodic and progressive, leading to extra-articular ankylosis of all major joints of the axial and appendicular skeleton, rendering movement impossible (FIG. 1a).
The earliest pathological finding in FOP is perivascular lymphocytic infiltration into normal-appearing skeletal muscle, followed by muscle-cell degeneration and highly vascular fibroproliferative soft tissue swelling. The fibroproliferative lesions evolve, through an endochondral process, into mature lamellar bone with marrow elements. Heterotopic ossifications are usually first detected around the spine and proximal extremities, then at multiple other places, which leads to dysfunction of articulations and often premature death.
FOP is a rare condition; the prevalence is ˜0.6/1 million live births. Reproductive fitness is low, and most cases appear to arise by spontaneous mutation. There is no effective treatment, and soft-tissue trauma (eg, biopsies, surgical procedures, intramuscular injections, or mandibular blocks for dental procedures) and viral illnesses are likely to induce episodes of rapidly progressive heterotopic ossification, with resultant permanent loss of motion in the affected area. Diagnostic errors with FOP are thought to be common and often associated with inappropriate and harmful diagnostic and therapeutic procedures Therefore, a reliable method is needed for an early diagnosis and treatment methods, thereby providing a foundation for development of treatments not only for FOP, but also for the more common disorders of osteogenesis.